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Targeting miRNA by CRISPR/Cas in cancer:advantages and challenges

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Military Medical Research 2024年第3期11卷 345-373页

作者： Bashdar Mahmud Hussen Mohammed Fatih Rasul Snur Rasool Abdullah Hazha Jamal Hidayat Goran Sedeeq Hama Faraj Fattma Abodi Ali Abbas Salihi Aria Baniahmad Soudeh Ghafouri-Fard Milladur Rahman mark C.Glassy Wojciech Branicki Mohammad Taheri Department of Biomedical Sciences Cihan University-ErbilErbilKurdistan Region 44001Iraq Department of Clinical Analysis College of PharmacyHawler Medical UniversityErbilKurdistan Region 44001Iraq Department of Pharmaceutical Basic Science Faculty of PharmacyTishk International UniversityErbilKurdistan Region 44001Iraq Medical Laboratory Science Lebanese French UniversityErbilKurdistan Region 44001Iraq Department of Biology College of EducationSalahaddin University-ErbilErbilKurdistan Region 44001Iraq Department of Medical Laboratory Science Komar University of Science and TechnologySulaymaniyah 46001Iraq Department of Medical Microbiology College of Health SciencesHawler Medical UniversityErbilKurdistan Region 44001Iraq Department of Biology College of ScienceSalahaddin University-ErbilErbilKurdistan Region 44001Iraq Center of Research and Strategic Studies Lebanese French UniversityErbil 44001Iraq Institute of Human Genetics Jena University Hospital07747 JenaGermany Department of Medical Genetics School of MedicineShahid Beheshti University of Medical SciencesTehran 374-37515Iran Department of Clinical Sciences MalmöSection for SurgeryLund University22100 MalmöSweden Translational Neuro-Oncology Laboratory San Diego(UCSD)Moores Cancer CenterUniversity of CaliforniaSan DiegoCA 94720USA Faculty of Biology Institute of Zoology and Biomedical ResearchJagiellonian University31-007 KrakówPoland Urology and Nephrology Research Center Shahid Beheshti University of Medical SciencesTehran 374-37515Iran

Clustered regulatory interspaced short palindromic repeats(CRISPR)has changed biomedical research and provided entirely new models to analyze every aspect of biomedical sciences during the last *** the study of cancer,the CRISPR/CRISPR-associated protein(Cas)system opens new avenues into issues that were once unknown in our knowledge of the non-coding genome,tumor heterogeneity,and precision ***/Cas-based geneediting technology now allows for the precise and permanent targeting of mutations and provides an opportunity to target small non-coding RNAs such as microRNAs(miRNAs).However,the development of effective and safe cancer gene editing therapy is highly dependent on proper design to be innocuous to normal cells and prevent introducing other *** study aims to highlight the cutting-edge approaches in cancer-gene editing therapy based on the CRISPR/Cas technology to target miRNAs in cancer ***,we highlight the potential challenges in CRISPR/Cas-mediated miRNA gene editing and offer advanced strategies to overcome them.

关键词： CRISPR CRISPR/Cas9 CRISPR/Cas12 Gene editing miRNAs Cancer therapy

Preventing roof fall fatalities during pillar recovery:A ground control success story

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International Journal of Mining Science and Technology 2017年第1期27卷 107-113页

作者： mark Christopher Gauna Michael MSHA Pittsburgh Safety and Health Technology CenterPittsburghPA 15236USA

For decades, pillar recovery accounted for a quarter of all roof fall fatalities in underground coal *** showed that a miner on a pillar recovery section was at least three times more likely to be killed by a roof fall than other coal miners. Since 2007, however, there has been just one fatal roof fall on a pillar line. This paper describes the process that resulted in this historic achievement. It covers both the key research findings and the ways in which those insights, beginning in the early 2000 s, were implemented in mining practice. One key finding was that safe pillar recovery requires both global and local *** stability is addressed primarily through proper pillar design, and became a major focus after the2007 Crandall Canyon mine disaster. But the most significant improvements resulted from detailed studies that showed that local stability, defined as roof control in the immediate work area, could be achieved with three interventions:(1) leaving an engineered final stump, rather than extracting the entire pillar,(2) enhancing roof bolt support, particularly in intersections, and(3) increasing the use of mobile roof supports(MRS). A final component was an emphasis on better management of pillar recovery *** included a focus on worker positioning, as well as on the pillar and lift sequences, MRS operations,and hazard identification. As retreat mines have incorporated these elements into their roof control plans,it has become clear that pillar recovery is not ‘‘inherently unsafe." The paper concludes with a discussion of the challenges that remain, including the problems of rib falls and coal bursts.

关键词： Retreat mining Roof support Room-and-pillar Ground control

Preventing aggressive prostate cancer with proven ：ardiovascular disease preventive methods

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Asian Journal of Andrology 2015年第6期17卷 874-877页

作者： mark A Moyad Department of Urology University of MichiganMedical Center 1500 East Medical Center DriveAnn Arbor MI 48109 USA

Cardiovascular disease （CVD） has been the number one cause of death in the U.S. for 114 of the last 115 years. Risk factors for prostate cancer have primarily mirrored risk proven risk factors for CVD, especially aggressive disease. Obesity, dyslipidemia, glucose intolerance, metabolic syndrome, unhealthy dietary habits or caloric excess, lack of physical activity, and inflammation are just some of these shared risk factors. The evidence also suggests proven CVD preventive measures are identical to prostate cancer preventive measures, especially in regard to aggressive disease. Thus, apart from lifestyle measures that can encourage optimal heart and prostate health there are potentially several dietary supplements that need to be avoided in healthy men because they may also increase the risk of prostate cancer. However, there are also several low-cost, generic, safe in the appropriate individuals, and naturally derived agents that could reduce prostate cancer risk, and these can be discussed and remembered utilizing the acronym S.A.M. （statins, aspirin, and/or metformin）.

关键词： Preventing aggressive methods

Halofuginone for fibrosis, regeneration and cancer in the gastrointestinal tract

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World Journal of Gastroenterology 2014年第40期20卷 14778-14786页

作者： mark Pines Institute of Animal Sciences the Volcani Center Bet Dagan 50250 Israel

Organ fibrosis and architectural remodeling can severely disrupt tissue function, often with fatal consequences. Fibrosis is the end result of chronic inflammatory reactions induced by a variety of stimuli, and the key cellular mediator of fibrosis comprises the myofibroblasts which, when activated, serve as the primary collagen-producing cells. Complex links exist between fibrosis, regeneration and carcinogenesis, and the concept that all organs contain common tissue fibrosis pathways that could be potential therapeutic targets is an attractive one. Because of the major impact of fibrosis on human health there is an unmet need for safe and effective therapies that directly target fibrosis. Halofuginone inhibits tissue fibrosis and regeneration, and thereby affects the development of tumors in various tissues along the gastrointestinal tract. The high efficacy of halofuginone in reducing the fibrosis that affects tumor growth and tissue regeneration is probably due to its dual role in inhibiting the signaling pathway of transforming growth factor β, on the one hand, and inhibiting the development of Th17 cells, on the other hand. At present halofuginone is being evaluated in a clinical trial for other fibrotic indication, and any clinical success in that trial would allow the use of halofuginone, also for all other fibrotic indications, including those of the gastrointestinal tract.

关键词： Stellate cell Myofibroblast Transforming growth factor β Extracellular matrix Cancer

Effect of music therapy on short-term psychological and physiological outcomes in mechanically ventilated patients:A randomized clinical pilot study

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Journal of Intensive Medicine 2024年第4期4卷 515-525页

作者： mark Ettenberger Rosangela Casanova-Libreros Josefina Chávez-Chávez Jose Gabriel Cordoba-Silva William Betancourt-Zapata Rafael Maya Lizeth Alexa Fandino-Vergara Mario Valderrama Ingrid Silva-Fajardo Sandra Milena Hernández-Zambrano SONO-Centro de Musicoterapia BogotáColombia Vice-Rectorate for Research Fundación Universitaria de Ciencias de la SaludBogotáColombia Department of Biomedical Engineering University of Los AndesBogotáColombia Department of Rehabilitation Sociedad de Cirugía de Bogotá Hospital de San JoséBogotáColombia Faculty of Nursing Fundación Universitaria de Ciencias de la SaludBogotáColombia

Background:Elevated anxiety levels are common in patients on mechanical ventilation(MV)and may challenge *** suggests music-based interventions may reduce anxiety during ***,studies inves-tigating specific music therapy techniques,addressing psychological and physiological well-being in patients on MV,are ***:This three-arm randomized clinical pilot study was conducted with MV patients admitted to the intensive care unit(ICU)of Hospital San Joséin Bogotá,Colombia between March 7,2022,and July 11,*** were divided into three groups:intervention group 1(IG1),music-assisted relaxation;intervention group 2(IG2),patient-preferred therapeutic music listening;and control group(CG),standard *** main outcome measure was the 6-item State-Anxiety *** outcomes were:pain(measured with a visual analog scale),resilience(measured with the Brief Resilience Scale),agitation/sedation(measured with the Richmond Agitation-Sedation Scale),vital signs(including heart rate,blood pressure,oxygen saturation,and respiratory rate),days of MV,extubation success,and days in the ***,three patients underwent electroencephalography during the ***:Data from 23 patients were analyzed in this *** age range of the patients was 24.0-84.0 years,with a median age of 66.0 years(interquartile range:57.0-74.0).Of the 23 patients,19 were female(82.6%).No statistically significant differences between the groups were observed for anxiety(P=0.330),pain(P=0.624),resilience(P=0.916),agitation/sedation(P=0.273),length of ICU stay(P=0.785),or vital signs.A statistically significant difference between the groups was found for days of MV(P=0.019).Electroencephalography mea-surements showed a trend toward delta and theta band power decrease for two patients and a power increase on both beta frequencies(slow and fast)in the frontal areas of the brain for one ***:In this pilot study,music therapy did not sig

关键词： Music therapy Mechanical ventilation Intensive care unit Anxiety Pain

Void fill and support techniques to stabilize drift excavated through a transition zone mined by a TBM at the Stillwater mine

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International Journal of Mining Science and Technology 2017年第1期27卷 71-76页

作者： Johnson Josh Jacobs Curt Ferster mark Tadolini Stephen Stillwater Mining Company NyeMT 59061USA Minova GeorgetownKYUSA

Stillwater Mining Company is the only U.S. producer of platinum group metals （PGMs） and the largest producer outside of South Afiica and Russia. The company controls a considerable portion of the J-M reef and is currently developing the ＂Blitz Project,＂ which will provide a main haulage level, ore pass systems, backfill plants, and fiow-through ventilation to increase production and ensure sustainable extraction of this critical strategic mineral. While driving two sub-parallel footwall laterals 8125 m in length, one of the development drifts experienced a massive fall in a geologically disturbed area created by a mafic dike intrusion. Combinations of a void fill material （Tekseal）, polyurethane injection, fore poling coupled with steel arches, and supplemental bolting allow safe and efficient advance through this geologically dis- turbed zone. This paper presents the details of this project.

关键词： TBM Ground Dike Cutterhead

Bleeder entry evaluation using condition mapping and numerical modeling

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International Journal of Mining Science and Technology 2021年第1期31卷 137-143页

作者： Ted M.Klemetti mark A.Van Dyke Gabriel S.Esterhuizen National Institute for Occupational safety and Health Pittsburgh Mining Research DivisionPittsburghPA 15236USA

One of the most common critical areas of longwall mining in terms of ground stability are the gateroad and bleeder *** critical entries provide much-needed safe access for miners and allow for adequate ventilation required for dilution of hazardous airborne contaminants and must remain open during mining of a multi-panel *** paper is focused on the stability of the longwall entries subjected to a single abutment load such as bleeders,first tailgate,and last *** tailgate and last headgate are also referred to as blind headgate and tailgate.A study of a longwall district through conditions mapping,support evaluations,and numerical modeling was conducted and evaluated by researchers from the National Institute for Occupational safety and Health(NIOSH).The condition mapping and support evaluations were performed on entries that spanned the previous five years of mining and relied on a diverse selection of supports to maintain the functionality of the *** modeling was also conducted to evaluate various support types with further investigation and comparison to the condition *** study demonstrated the importance of the abutment load decay versus distance from the gob edge,the potential for a reduction in material handling related injuries,as well as optimal usage of secondary and standing support.

关键词： Stability assessment Bleeder entry Abutment loading Condition mapping Longwall Ground control

Virtual flight test techniques to predict a blended-wing-body aircraft in-flight departure characteristics

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Chinese Journal of Aeronautics 2022年第1期35卷 215-225页

作者： Junquan FU Zhiwei SHI Zheng GONG mark HLOWENBERG Dawei WU Lijun PAN Nanjing University of Aeronautics and Astronautics Nanjing 210016China University of Bristol Bristol BS81TRUnited Kingdom CO MAC Shanghai Aircraft Design and Research Institute Shanghai 201210China

As one of the promising configurations of the next generation of commercial aircraft,research on departure characteristics of the Blended-Wing-Body(BWB)is of great signification to safe flight limits.A three-degree-of-freedom(3-DOF)virtual flight test in a wind tunnel has been implemented for a candidate configuration to predict the departure *** support mechanism,the test model and the control law of the virtual flight test are *** order to show the relationship between virtual flight test and actual flight test,the similarity criterion is also *** open loop,the model has mild oscillations in the longitudinal and lateral directions,which are stable in *** effect of flight control has been verified in virtual flight and actual subscale flight *** analysis of system identification results indicate that the model has a good response to the excitation signal,and the response is in reasonable agreement with the flight ***,the virtual flight departure test results are compared with the flight *** shows that there is a good correspondence between the angle of attack and the elevator deflection at *** gives promising evidence of the practicability of virtual flight testing to predict departure of a BWB.

关键词： Blended-wing-body Departure Flight test Similarity criterion Virtual flight test

Ketamine and midazolam sedation for pediatric gastrointestinal endoscopy in the Arab world

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World Journal of Gastroenterology 2011年第31期17卷 3630-3635页

作者： Mohamad-Iqbal S Miqdady Wail A Hayajneh Ruba Abdelhadi mark A Gilger Pediatric Department Medical SchoolJordan University of Science and Technology Pediatric Institute Sheikh Khalifa Medical Citymanaged by Cleveland ClinicAbu Dhabi Pediatric Department University of Texas Health Science CenterSan AntoniaTXSan Antonia Pediatric Department Baylor College of Medicine

AIM:To evaluate the safety and effectiveness of intravenous ketamine-midazolam sedation during pediatric endoscopy in the Arab ***:A retrospective cohort study of all pediatric endoscopic procedures performed between 2002-2008 at the shared endoscopy suite of King Abdullah University Hospital,Jordan University of Science & Technology,Jordan was *** children were > 1 year old and weighed > 10 kg with American Society of Anesthesiologists class 1 or *** was performed in terms of sedation-related complications(desaturation,respiratory distress,apnea,bradycar-dia,cardiac arrest,emergence reactions),adequacy of sedation,need for sedation reversal,or failure to complete the ***:A total of 301 patients(including 160 males) with a mean age of 9.26 years(range,1-18 years) were *** were premedicated with atropine;and 79.4%(239/301) had effective and uneventful *** 248(82.4%) of the 301 patients received a mean dose of 0.16 mg/kg(range,0.07-0.39) midazolam and 1.06 mg/kg(range,0.31-2.67) ketamine,respectively within the recommended dosage *** maximum midazolam dose was exceeded in 17.6% patients [34 female(F):19 male(M),P = 0.003] and ketamine in 2.7%(3 M:5 F).Maximum midazolam dose was more likely to be exceeded than ketamine(P safe and effective for diagnostic pediatric gastrointestinal endoscopy in the Arab world for children aged > 1 year and weighing > 10 kg without co-morbidities.

关键词： Pediatric endoscopy Sedation Ketamine Arab